cholecalciferol on depressive symptoms in type 2 diabetes mellitus patients

Conditions: Diabetes Mellitus, Type 2; Depressive Symptoms

Summary: one in eleven adults falls ill with diabetes mellitus (dm) and 90% of them suffered from type 2 dm. depression in type 2 dm patients had a big impact, acting as a major barrier to self-care in type 2 dm patients. depression in diabetes patients is also associated with decreasing quality of life. poor self-care behavior and adherence, poor glycemic control, and increased risk of mortality about 36-38% from cardiovascular complications are other known debilitating results. vitamin d receptors are present in many organ systems, namely the pancreas, intestine, musculoskeletal, and nervous systems. vitamin d has pleiotropic effects, which were seen from its mechanism as an anti-inflammatory, anti-apoptotic, and immunomodulatory agent. based on the mechanism of vitamin d action in the nervous system, which also plays a role in depression pathogenesis, vitamin d is hypothesized to have a beneficial effect on depression, both for depression prevention and treatment. few studies denote that vitamin d can improve depression in type 2 dm patients. vitamin d may become an important adjuvant therapy to ameliorate depression in type 2 dm patients. these clinical trials concerning vitamin d in type 2 dm are relevant, reminding that type 2 dm resulted in higher morbidity, mortality, and numerous high-risk complications in the population.

according to world health organization report's, depression was estimated causing distress in most people on 2030. 1 in indonesia, the prevalence of depression in 2017 was 3,7%.2 depression often found in internal medicine patient's as a comorbid in various chronic diseases. 3 one of the most common chronic disease is type 2 diabetes mellitus. there's one in eleven adults suffered from diabetes mellitus, and 90% of them had type 2 diabetes mellitus (dm). basic health research data on 2018 showed there were 10.9% case type 2 dm in indonesia. 4 dki jakarta province had 3,4% or 11.226 people aged 15 years and over with diabetes mellitus and had been a highest prevalence of diabetes mellitus among population aged 15 years and over. meanwhile, prevalence of depression among adults aged 15 and over in dki jakarta was 5.9%. seminkovics k et al5 reported one in four people with type 2 diabetes mellitus suffered from depression in united states. in indonesia, nasrun wms6 reported there were 27,6% prevalence of depression in type 2 diabetes mellitus patients's with cognitive impairment, while arshita et al7 found there were 60% patients with depression in type 2 diabetes mellitus patients with pedic ulcers in rscm . depression in type 2 diabetes mellitus patients had a big impact, such as: depression can be a major barrier to self-care in type 2 diabetes mellitus patients. 1,5 depression in diabetes patients is also associated with decreasing quality of life. 6 poor of self-care behavior and adherence, poor of glycemic control, and increased risk of mortality about 36-38% from cardiovascular complication are other known debilitating results. 8 vitamin d receptors are present in various organs such as the pancreas, intestine, musculoskeletal, and nervous system. vitamin d has a pleiotrophic effect which were seen from its mechanism as anti-inflammatory, anti-apoptotic, and immunomodulatory. 16 based on mechanism of vitamin d action in nervous system, which also plays a role in the depression pathogenesis, vitamin d is hypothesized to have a beneficial effect on depression, both for prevention and treat the pathomechanism. the protective effect of vitamin d for prevent depression had been widely studied in copious observational epidemiological studies, although with diversified results. many studies have been conducted to assess the beneficial effects of vitamin d on a variety outcomes including depression, which are summarized in systematic reviews and meta-analyzes of observational studies. a meta-analyses by ju sy et al38 found that low plasma 25 (oh) d levels were associated with and increased risk of depression in a cross sectional study with 43,1377 participants. vitamin d deficiency is a worldwide health problem. vitamin d had known as an important role in biological processes, calcium homeostasis, and various health problems. in addition to its role in musculoskeletal, vitamin d is also associated with a few non-musculoskeletal diseases such as immunity, cancer, cardiovascular disease, hypertension, diabetes, and psychological problems like dementia or depression. 17 both vitamin d and its analogues are natural ligands for vitamin d receptor (vdr). vitamin d receptors are widely distributed throughout body including brain and pancreas. vitamin d receptors found in cerebellum, hippocampus, substantia nigra, basal forebrain, prefrontal cortex and hypothalamus. this explains the role of vitamin d in brain development and emotional disorders. in brain development, vitamin d played role in proliferation and differentiation of neuron cells. in adult brain, vitamin d played a role in neurogenesis in the hippocampus and synthesizes neurotransmitters such as dopamine, gaba, and serotonin. 18 it's known as depression neurotransmitter. other studies showed that vitamin d might repair neurotransmitters, inflammation, metabolic, and oxidative stress. cholecalciferol will activate 1-α hydroxylase enzymes and p450 cytochrome, which transformed calcifediol hydroxylation into activated vitamin d in central nervous system, so that improving depression. anti depressants such as ssris (selective serotonin reuptake inhibitors), can induce gastrointestinal bleeding in patients whose taking anti-platelets or anti-coagulants, increase weight and dyslipidemia. thus, other studies therapy based on pathogenesis of depression, effective and side effects need to be done. few studies denote that vitamin d can improve depression in type 2 dm patients. those studies used only beck depression inventory test to assess depression without any biological markers. vitamin d may become an important adjuvant therapy to ameliorate depression in type 2 dm. these clinical trials concerning vitamin d in type 2 dm are relevant, reminding that type 2 dm resulted in higher morbidity, mortality and numerous high risk complication in the population. methods/design: this is a prospective, randomized, double blind, and controlled clinical study to investigate the effects of cholecalciferol on depressive symptoms in type 2 diabetes mellitus patients. patients included into the study will be randomized into two groups and receive placebo (as control group) or cholecalciferol administered orally for 3 months. discussion : vitamin d may become an important adjuvant therapy to ameliorate depression in type 2 dm patients. thus, type 2 diabetes mellitus with depression symptoms will have a better quality of life.

Eligibility criteria:
inclusion criteria: * male or female subjects with aged 18 and over * living in around jakarta * type 2 diabetes mellitus patients with depression symptom * patients with body mass index 20-30 m/kg2 * patients are able and willing to maintain diet, physical activity, and lifestyle for 3 months * patients are able and willing to control for follow up exclusion criteria: * - presence of severe hepatic dysfunction, defined as cirrhosis hepatic * presence of severe renal dysfunction, defined as chronic kidney disease stage 5 or e-gfr ≤15 or history of hemodialysis * patients with acute coronary syndrome * presence of acute systemic inflammatory response syndrome (sirs). the term sirs describes a clinical state arising from a non-specific cause, infective, or otherwise * recent obtained vitamin d therapy within the last 3 months * current or regular use of corticosteroids within immunosuppressant dosage * presence of major depression * presence of psychosis * current or regular use of anti-depressant * current or regular use of phenytoin or phenobarbital * for females: current pregnancy and lactation period * patients who refuse the studies

Keywords: diabetes mellitus, type 2 depression cholecalciferol